“The Importance of PET/CT in Human Health”

Homer A. Macapinlac, M.D.

Learning objectives

• Provide an overview of the impact of PET/CT imaging on the management of patients and its impact on health care expenditures.

• Review the current use of PET/CT in the multi-disciplinary care of oncology patients, with emphasis on its utility in adaptive therapeutic strategies.

Summary

• FDG PET/CT impacts the management of patients in nearly all solid tumors.

• In USA, reduction in reimbursement of FDG PET/CT, reduced utilization and its cost remains low compared to total cost of care

• Novel tracers approval requires large randomized trials to prove survival benefit.

Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, Jerin J, Young J, Byars L, Nutt R.

A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000 v41:1369-79.

FIGURE 5.

78-y-old man with NSCCa of the lung. (A) Large isodense mass seen on CT.

(B) PET scan shows a hypermetabolic

rim of increased FDG uptake, with necrotic center.

(C) Fused image shows good alignment of 2 modalities. Lymph node in mediastinum (arrow) also demonstrated increased FDG uptake.

Global Cancer Problem

• 14.1 million cancer cases and 8.2 million cancer deaths occurred in 2012 worldwide

• Economically developing world account for: – 56% of the cases – 64% of the deaths

• By 2030: 21.7 million cancer cases per year – 13 million cancer deaths – 60-70 % of cases in developing world

Global Cancer Facts • Lung cancer most common in

men globally • Prostate ca most common in

developed countries • Breast ca is most common

type among women – 1.7 m new, 0.5 m deaths – Lung ca is most common cause

of death in women surpassing breast ca in dev’ed countries

• 23% of ca due to infection in developing countries (vs7%) – Vaccination, treatment,

behavioral change • Tobacco: 6 m deaths/yr • Hep B vaccination, Cervical Ca

screening are best buys

Multi-Disciplinary Care From Modality to Disease Based Practice

• Radiology/Fluoroscopy • CT • MRI • Nuclear Medicine • Ultrasound • Interventional

• Thoracic Oncology • GI Oncology • Pediatric Oncology • Breast Oncology • GU Oncology • Etc…

Clinical Importance of PET/CT is to provide an imaging consultation!

• Answer the most important question. – Is cancer present or absent? – Direct or avoid biopsy? – Triage the management!

• In a patient who finished treatment for cancer – NED (follow conservatively) – Recurrence (Direct biopsy then decide therapy)

• In a patient undergoing multimodality therapy – Same, better or worse?

National Oncologic PET Registry Results

Overall Impact on Patient Management – Diagnosis, Staging, Restaging, Recurrence – Data on 22,975 scans from May 8, 2006 – May 7, 2007 – J Clin Oncol 2008; 26:2155-61

Treatment Monitoring – Data on 10,447 scans from May 8, 2006 – Dec 31, 2007 – Cancer 2009:115:410-18

Impact on Patient Management for by Cancer Type – Staging, Restaging, Recurrence (proven cancer type) – Data on 40,863 scans from May 8, 2006 – May 7, 2008 – J Nucl Med 2008; 49:1928-35

FDG PET for Solid Tumors and Myeloma

Tumor Type

Initial Treatment Strategy (formerly “diagnosis” &

“staging”)

Subsequent Treatment Strategy (formerly “restaging” and “monitoring response to

treatment”) Colorectal Cover Cover Esophagus Cover Cover Head and Neck (not thyroid or CNS)

Cover Cover

Lymphoma Cover Cover Non-small cell lung Cover Cover Ovary Cover Cover Brain Cover Cover Cervix Cover with exceptions * Cover Small cell lung Cover Cover Soft tissue sarcoma Cover Cover Pancreas Cover Cover Testes Cover Cover Prostate Non-cover Cover Thyroid Cover Cover Breast (male and female) Cover with exceptions * Cover Melanoma Cover with exceptions * Cover All other solid tumors Cover Cover Myeloma Cover Cover All other cancers not listed Cover Cover

CMS Covered Indications for FDG PET

• Three (3) FDG-PET scans will be nationally covered for oncologic indications when used to guide subsequent physician management of anti-tumor strategy after initial anticancer therapy.

• Additional scans will be permitted at MAC or MA Plan Contractor discretion.

Medical Imaging: Decline in Utilization and Spending

• Past decade imaging expenditures rose at a much faster rate than other medical services

• lower payments by CMS, Radiology benefit managers (RBM), Clinic decision support (CDS)

• Maturation of advanced imaging techniques • Patient radiation safety awareness • Appropriateness Criteria and Clinical

Utilization Guidelines

Fig. 4 Annual percentage changes in Medicare Part B program spending per enrollee for medical imaging. <ce:source> Source: Medicare Part B (fee-for-service) Physician/Supplier Procedure Summary data files. DRA = Deficit Reduction Act of 2005.</ce:source>

Martey S. Dodoo , Richard Duszak Jr , Danny R. Hughes

Trends in the Utilization of Medical Imaging From 2003 to 2011: Clinical Encounters Offer a Complementary Patient-Centered Focus

Journal of the American College of Radiology, Volume 10, Issue 7, 2013, 507 - 512

http://dx.doi.org/10.1016/j.jacr.2013.02.023

USA Clinical PET/CT 2014 • 1.62 million/yr – 13% net decrease from 2011 *

– (81.2 million CT’s, 7% higher than 2013) – PET-10k (1981), 20k (1991), 2011 (1.9 million)

• 2,350 sites using fixed or mobile PET, PET/CT or PET/MR* • 95% radiopharmaceuticals – outside supplier

– FDG: 96%, Rubidium 2%

• 94% of all PET studies in 2012 were for cancer: – Dx 19%, staging 38%, Rx plan 13%, follow-up 30% – Top indications: lung, lymphoma, breast, colon – Neurology and cardiology = 6% of procedures

*IMV's 2014 PET Imaging Market Summary Report (http://www.imvinfo.com)

Section of PET Total Number of Scans – 19000

FY14 Distribution

Cost to outcomes issue

• FDG PET reimbursement has gone down (50%) – 1.5% of the total costs of cancer care – Appropriate use can reduce cost of cancer care

• CMS, won’t reimburse new radiotracers because there have not been large enough clinical trials to show that the tracer changes management of patients or improves outcomes. Do they live longer? Prove it.

J Nucl Med 2011; 52:86S–92S

Hodgkin’s Lymphoma: Initial and subsequent treatment strategies

• Before: CXR, CECT, Ga67, RNCA, MR – Subsequent repeat everything at end of Rx

• Current: FDG PET/CT, (Lugano), CECT (non FDG avid) – Subsequent: FDG PET/CT end of Rx – Mid cycle (Deauville Criteria)

• Change: FDG PET/CT replaced Ga67, CECT • Biopsy Deauville 4-5: (+) refractory, (-) short interval PET 3-6 months for

up to 12 months until Deauville 1-2. • less CECT, MR for brain/spine, Less RNCA (US), CXR

• Practice change: early response assessment, change management, predict outcome

Lugano Classification: Initial evaluation and staging of HL and NHL patients

• FDG PET/CT is the standard for FDG-avid lymphomas, CT is for non-avid histology.

• Modified Ann Arbor terminology for anatomic distribution of disease. A/B suffixes for HL.

• If PET-CT is done, BM biopsy is not indicated for HL/DLBCL. Biopsy if PET (-) or discordant.

• Treatment based on limited (I &II, non-bulky) or advanced (III or IV) disease.

J Clin Oncol. 2014 Sep 20;32(27):3059-68.

Lugano Classification: Response assessment of HL and NHL patients

• PET-CT is to be used to assess response in FDG-avid histologies using the 5-point scale; CT is preferred for low or variable FDG avidity.

• Complete metabolic response is considered a complete remission even with persistent mass

• PR requires a decrease > 50% in sum of the product of perpendicular diameters of up to six representative nodes or extranodal lesions.

J Clin Oncol. 2014 Sep 20;32(27):3059-68.

Lugano Classification: Response assessment of HL and NHL patients

• PD on CT criteria requires only increase in the perpendicular diameters of single node ≥ 50%.

• Surveillance scans after remission discouraged particularly for HL and DLBCL; repeat scans may be considered in cases of equivocal findings after treatment.

• Judicious use of follow-up scans considered in indolent lymphomas with residual intra-abdominal or retroperitoneal disease.

J Clin Oncol. 2014 Sep 20;32(27):3059-68.

15 year old female Nodular sclerosing HL stage IIB

Baseline 6 weeks post-tx

15 year old female NSHL stage IIB

Baseline 6 weeks post-tx

15 year old female NSHL stage IIB

Baseline 6 weeks post-tx

Deauville PET Criteria SCORE PET/CT SCAN RESULT

1 NO UPTAKE ABOVE BACKGROUND

2 UPTAKE </= MEDIASTINUM

3 UPTAKE > MEDIASTINUM BUT < LIVER

4* UPTAKE MODERATELY INCREASED COMPARED TO THE LIVER AT ANY SITE

5* UPTAKE MARKEDLY INCREASED COMPARED TO THE LIVER AT ANY SITE

X NEW AREAS OF UPTAKE UNLIKELY RELATED TO LYMPHOMA

Barrington SF, et al. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging(2010):37:1824-1833. *Biopsy

The prognostic value of interim PET scan in patients with classical Hodgkin lymphoma.

• The prognostic value of interim FDG PET was evaluated after 2 cycles of ABVD in classical HL patients (n = 229), based on Deauville criteria.

• 3 NM MD’s blinded for clinical information except for initial PET – Unanimous agreement for final interpretation in 95% of cases

• 3-year PFS in PET2-negative vs. PET2-positive

– early stage non-bulky disease 95·9% vs. 76·9% (P < 0·0018) – bulky stage II disease 83·3% vs. 20·0% (P = 0·017) – advanced stage IPS ≤2 77·0% vs. 30·0% (P < 0·001) – advanced stage IPS ≥3 71·0% vs. 44·4%(P = 0·155)

• The outcome after positive PET2 was better than previously reported. The

results from non-randomized studies of PET2-guided therapy would be valuable with careful interpretation.

Br J Haematol. 2014 Apr;165(1):112-6

Screening and Randomization.

Radford J et al. N Engl J Med 2015;372:1598-1607

Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s Lymphoma

• RAPID was designed to determine whether patients with clinical stage IA or stage IIA Hodgkin’s lymphoma and negative PET findings after three cycles of ABVD require consolidation radiotherapy.

• The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival.

• Nevertheless, patients in this study with early-stage Hodgkin’s lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy.

N Engl J Med, Volume 372(17):1598-1607 April 23, 2015

Follicular Lymphoma

4 cycles R-CHOP 2 cycles R-ESHAP 2 cycles R-hyperCVAD

34 year old woman relapsed DLBCL small bowel bx

CD19 CAR T cell Rx

Therapeutic Targeting of the Hallmarks of cancer

Hanahan and Weinberg Cell. 2011 Mar 4;144(5):646-74.

Summary

• FDG PET/CT impacts the management of patients in nearly all solid tumors.

• In USA, reduction in reimbursement of FDG PET/CT, reduced utilization, and its cost remains low compared to total cost of care.

• Novel tracers approval requires large randomized trials to prove survival benefit.

www.mdanderson.org • www.mdanderson.org/ask 1-877-MDA-6789